Young onset diabetic subjects in tropical developing countries include a group of subjects who exhibits a characteristic
ketosis resistance termed as
Malnutrition Related
Diabetes Mellitus (MRDM) by the WHO Study Group. The mechanism for this resistance to
ketosis is still uncertain. To understand this mechanism we have studied the serum responses of
glucose, non-
esterified fatty acid (
NEFA) and
triglyceride (TG) to
intravenous fat emulsion in newly diagnosed 8 fibrocalculous pancreatic diabetes (FCPD) and 11 low
insulin secretory (LIS) subjects under 30 years of age along with 27 age-matched
Non Insulin Dependent Diabetes Mellitus (
NIDDM) subjects. Overnight fasting subjects were given a 90 min infusion of intralipos 10% (2.5 mg/kg
body weight/min) and serum was collected at 0, 60, 90, 120 and 150 min. The fasting
NEFA in the 3 groups were almost similar (micromol/l, M +/- SEM: 486 +/- 58, 564 +/- 76 and 559 +/- 34 in FCPD, LIS and
NIDDM respectively). Fasting TG also showed a close similarity among 3 groups (mg/dl, M+/-SEM: 117 +/- 11, 110 +/- 22 and 123 +/- 4 in FCPD, LIS and
NIDDM respectively). Intravenous fat caused a steady rise of
NEFA as well as TG in all groups during the 90 minutes of infusion followed by a gradual fall. No two groups significantly differed regarding
NEFA and TG at any time point. Fasting
glucose was markedly higher in FCPD (22.9 +/- 2.5, mmol/l, M+/-SEM) and LIS (20.8 +/- 1.6) than
NIDDM (11.0 +/- 1.0). In all the 3 groups
glucose showed a slow but steady fall. Fasting
C-peptide was very low in FCPD (0.42 +/- 0.08, ng/ml, M +/- SEM) and LIS (0.55 +/- 0.09) whereas it was within normal range in
NIDDM patients (2.99 +/- 0.24). The results suggest the following: (a) Depleted body fat store do not lead to a decreased supply of
NEFA in FCPD and LIS subjects at the fasting state; (b) Increased supply of
NEFA in these subjects lead to a normal esterification response as evidenced by a parallel rise of TG; (c) Inspite of markedly low level of the antilipolytic
hormone insulin, FCPD and LIS subjects are capable to maintain
NEFA and TG responses similar to
NIDDM subjects. This may indicate that factor (s) other than substrate and esterification is (are) probably involved in the
ketosis resistance of FCPD and LIS subjects; and (d) Although FCPD and LIS differ regarding generalized pancreatic damage (which raises the possibility of involvement of
glucagon producing alpha-cells in the FCPD group) the two groups do not differ regarding the ketogenic substrate and esterfication responses.